Laboratory of Reproductive Toxicology and Molecular Biology, Department of Medicine, State University of Centro-Oeste (UNICENTRO), Alameda Élio Antonio Dalla Vecchia, 838, Zip-Code, 85040-167, Parana, Brazil.
Laboratório de Toxicologia Celular, Departamento de Biologia Celular, Universidade Federal Do Paraná, CEP 81.531-980, Curitiba, PR, Brazil.
Environ Pollut. 2023 Oct 1;334:122132. doi: 10.1016/j.envpol.2023.122132. Epub 2023 Jul 4.
The increased prevalence of human infertility due to male reproductive disorders has been linked to extensive exposure to chemical endocrine disruptors. Acrylamide (AA) is a compound formed spontaneously during the thermal processing of some foods that are mainly consumed by children and adolescents. We previously found that prepubertal exposure to AA causes reduced sperm production and functionality. Oxidative stress is recognized as the main cause of reduced sperm quality and quantity. In this sense, our objective was to evaluate the expression and activity of genes related to enzymatic antioxidant defense, nonprotein thiols, lipid peroxidation (LPO), protein carbonylation (PC) and DNA damage in the testes of rats exposed to acrylamide (2.5 or 5 mg/kg) from weaning to adult life by gavage. For the AA2.5 and AA5 groups, there were no alterations in the transcript expression of genes related to enzymatic antioxidant defense. The enzymatic activities and metabolic parameters were also not affected in the AA2.5 group. For the AA5 group, the enzymatic activities of G6PDH and GPX were reduced, SOD was increased, and protein carbonylation (PC) was increased. Data were also evaluated by Integrate Biomarker Response (IBRv2), a method to analyze and summarize the effects on biomarkers between doses. The IBRv2 index was calculated as 8.9 and 18.71 for AA2.5 and AA5, respectively. The following biomarkers were affected by AA2.5: decreased enzymatic activities of G6PDH, SOD, and GPX, increased GST and GSH, increased LPO and PC, and decreased DNA damage. For AA5, decreased enzymatic activities of G6PDH, GST, CAT and GPX, increased SOD and GSH, increased PC, and decreased LPO and DNA damage were observed. In conclusion, AA exposure during the prepubertal period causes imbalances in the testicular enzymatic antioxidant defense, contributing to the altered spermatic scenario in the testes of these rats.
由于男性生殖障碍导致的人类不育症的患病率不断上升，这与广泛接触化学内分泌干扰物有关。丙烯酰胺（AA）是一种在某些主要被儿童和青少年食用的食品的热加工过程中自发形成的化合物。我们之前发现，青春期前接触 AA 会导致精子生成和功能减少。氧化应激被认为是精子质量和数量减少的主要原因。在这种情况下，我们的目标是评估暴露于丙烯酰胺（2.5 或 5mg/kg）的大鼠从断奶到成年期通过灌胃的方式接触 AA 时，睾丸中与酶抗氧化防御、非蛋白巯基、脂质过氧化（LPO）、蛋白质羰基化（PC）和 DNA 损伤相关的基因的表达和活性。对于 AA2.5 和 AA5 组，与酶抗氧化防御相关的基因的转录表达没有改变。AA2.5 组的酶活性和代谢参数也没有受到影响。对于 AA5 组，G6PDH 和 GPX 的酶活性降低，SOD 增加，蛋白质羰基化（PC）增加。数据还通过整合生物标志物反应（IBRv2）进行了评估，IBRv2 是一种分析和总结剂量间生物标志物效应的方法。AA2.5 和 AA5 的 IBRv2 指数分别为 8.9 和 18.71。AA2.5 影响了以下生物标志物：G6PDH、SOD 和 GPX 的酶活性降低，GST 和 GSH 增加，LPO 和 PC 增加，DNA 损伤减少。对于 AA5，观察到 G6PDH、GST、CAT 和 GPX 的酶活性降低，SOD 和 GSH 增加，PC 增加，LPO 和 DNA 损伤减少。总之，青春期前接触 AA 会导致睾丸酶抗氧化防御失衡，导致这些大鼠睾丸中精子发生情况发生改变。
